Analyses of function and primary structure of hemoglobins from representative nonhuman primates will be carried out with the intention of reconstructing the course of evolutionary divergence of beta- from gamma-chain genes that occurred during the period of transition from lower (prosimian) to higher (anthropoid) primates. In addition, it is anticipated that such studies will provide insight into the nature of the advantages gained by relegation of the synthesis of gamma chains to the fetal stage of the life cycle and into the origins of the multiple gamma-chain loci in man. Recent studies indicate that there is, in addition to the linked A gamma and G gamma genes for human fetal hemoglobin, a TG gamma gene whose activity may be preferentially elevated in persons who have the gene in common with any of several hereditary and acquired conditions typically associated with elevated levels of fetal hemoglobin. Analyses of the Hbs F in members of control populations and in persons with such conditions as sickle-cell anemia, beta thalassemia and hypoplastic anemia will permit estimates of TG gamma-gene activities in the patient and nonpatient populations. Discrepancies in the proportions of persons in these groups who synthesize TG gamma chains might indicate that TG gamma-gene activity is inducible. Investigations of TG gamma inducibility by erythropoietin will be conducted, using gamma chains synthesized in cultured bone marrows and the Hbs F from periodically phlebotomized sicklemics. The possibility of induction of gamma-gene activity will also be examined in pregnant and anemic monkeys known to bear duplicate gamma-chain loci.